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Comparing the in vivo sonodynamic effects of dual- and single-frequency ultrasound in breast adenocarcinoma

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An Erratum to this article was published on 08 August 2012

Abstract

Introduction

Dual-frequency ultrasound has recently been shown to extensively enhance the acoustic cavitation yield in water.

Methods

In this study, the in vivo antitumor effect of simultaneous, dual-frequency ultrasound at low-level intensity (I SATA = 2 W/cm2 for 1 MHz and I SATA = 0.2 W/cm2 for 150 kHz) in combination with an intravenous injection of 5 mg/kg hematoporphyrin (Hp) was investigated in a model of breast adenocarcinoma in Balb/c mice. Seventy-one tumor-bearing mice were divided into nine treatment groups: control, sham, Hp injection, and single- and dual-frequency sonication in the presence and absence of Hp. The tumor growth delay was then calculated based on the tumor volume at various times after treatment using the following parameters: relative volume percent, \( T_{5} \) and \( T_{2} \) times (to reach five and two times the initial volume), percent of tumor growth inhibition ratio, and survival period.

Results

Our results showed no significant difference between the 150 kHz and 1 MHz single-frequency groups when compared with the sham group after 9 days of treatment (p > 0.05). However, treatment with dual-frequency ultrasound significantly delayed tumor growth when compared with the sham group (p < 0.05) after 9 days of treatment. Furthermore, in vivo experiments showed that combined dual-frequency sonication controlled tumor growth more effectively than single-frequency sonication. Evaluation of the therapeutic effects of single- and dual-frequency ultrasound in sonodynamic therapy revealed that treatment with the combination of dual-frequency ultrasound and Hp resulted in a significant reduction in the relative volume percent of tumors after 3 days of treatment (p < 0.05) compared with the controls. Additionally, the T 5 time and the survival period in the group treated with the combination therapy was significantly longer than those in all the other groups (p < 0.05). These findings were further verified histopathologically.

Conclusion

In conclusion, our results reveal that sonodynamic therapy using dual-frequency ultrasound is able to extend the survival time of animals compared with single-frequency sonication.

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References

  1. Liu Q, Li X, Xiao L, Wang P, Wang X, Tang W. Sonodynamically induced antitumor effect of hematoporphyrin on Hepatoma 22. Ultrason Sonochem. 2008;15:943–8.

    Article  PubMed  CAS  Google Scholar 

  2. Yumita N, Nishigaki R, Umemura S. Sonodynamically induced antitumor effect of Photofrin II on colon 26 carcinoma. J Cancer Res Clin Oncol. 2000;126:601–6.

    Article  PubMed  CAS  Google Scholar 

  3. Yumita N, Umemura S. Sonodynamic therapy with Photofrin II on AH130 solid tumor. Cancer Chemother Pharmacol. 2003;51:174–8.

    PubMed  CAS  Google Scholar 

  4. Tomankova K, Kolarova H, Kolar P, Kejlova K, Jirova D. Study of cytotoxic effect of photodynamically and sonodynamically activated sensitizers in vitro. Toxicol In Vitro. 2009;23:1465–71.

    Article  PubMed  CAS  Google Scholar 

  5. Bailey MR, Khokhlova VA, Sapozhnikov OA, Kargl SG, Crum LA. Physical mechanisms of the therapeutic effect of ultrasound: a review. Acoust Phys. 2003;49:369–88.

    Article  Google Scholar 

  6. Umemura S, Yumita N, Nishigaki R, Umemura K. Mechanism of cell damage by ultrasound in combination with hematoporphyrin. Jpn J Cancer Res. 1990;81:962–6.

    Article  PubMed  CAS  Google Scholar 

  7. Barnett S. Cavitation—its nature, detection and measurement. Ultrasound Med Biol. 1998;24:S11–21.

    Article  Google Scholar 

  8. Neppiras EA, Noltingk BE. Cavitation produced by ultrasonics: theoretical conditions for the onset of cavitation. Proc Phys Soc. 1951;12:1032–8.

    Google Scholar 

  9. Laborde JL, Bouyer C, Caltagirone JP, Gerard A. Acoustic cavitation field prediction at low and high frequency ultrasounds. Ultrasonics. 1998;36:581–7.

    Article  CAS  Google Scholar 

  10. Liu HL, Hsieh CM. Single transducer dual frequency ultrasound generation to enhance acoustic cavitation. Ultrason Sonochem. 2009;16:431–8.

    Article  PubMed  CAS  Google Scholar 

  11. Barati AH, Mokhtari-Dizaji M, Mozdarani H, Bathaie SZ, Hassan ZM. Effect of exposure parameters on cavitation induced by low level dual frequency ultrasound. Ultrason Sonochem. 2007;14:783–9.

    Article  PubMed  CAS  Google Scholar 

  12. Brotchie A, Grieser F, Ashokkumar M. Sonochemistry and sonoluminescence under dual frequency ultrasound irradiation in the presence of water soluble solutes. J Phys Chem C. 2008;112:10247–50.

    Article  CAS  Google Scholar 

  13. Zheng H, Mukdadi O, Kim H, Hertzberg JR, Shandas R. Advantages in using multifrequency excitation of contrast microbubbles for enhancing echo particle image velocimetry techniques: initial numerical studies using rectangular and triangular waves. Ultrasound Med Biol. 2005;31:99–108.

    Article  PubMed  Google Scholar 

  14. Servant G, Laborde JL, Hita A, Caltagirone JP, Gerard A. On the interaction between ultrasound waves and bubble clouds in mono and dual frequency sonoreactors. Ultrason Sonochem. 2003;10:347–55.

    Article  PubMed  CAS  Google Scholar 

  15. Iernetti G, Ciuti P, Dezhkunov NV, Reali M, Francescutto A, Johri GK. Enhancement of high frequency acoustic cavitation effects by a low frequency stimulation. Ultrason Sonochem. 1997;4:263–8.

    Article  Google Scholar 

  16. Tachibana K, Feril LB Jr, Ikeda-Dantsuji Y. Sonodynamic therapy. Ultrasonics. 2008;48:253–9.

    Article  PubMed  CAS  Google Scholar 

  17. Rosenthal I, Sostaric JZ, Riesz P. Sonodynamic therapy: a review of the synergistic effects of drugs and ultrasound. Ultrason Sonochem. 2004;11:349–63.

    PubMed  CAS  Google Scholar 

  18. Kessel D, Jeffers R, Fowlkes JB, Cain C. Porphyrin-induced enhancement of ultrasound cytotoxicity. Int J Radiat Biol. 1994;66:221–8.

    Article  PubMed  CAS  Google Scholar 

  19. Warthington AE, Thompson J, Lalonde R, Patterson M, Rauth AM, Hunt JW. Mechanism of ultrasound enhanced porphyrin cytotoxcity: free radical and hematoporphyrin effect. Ultrasound Med Biol. 1997;23:1095–105.

    Article  Google Scholar 

  20. Yumita N, Okuyama N, Sasaki K, Umemura S. Sonodynamic therapy on chemically induced mammary tumor: pharmacokinetics, tissue distribution and sonodynamically induced antitumor effect of porfimer sodium. Cancer Sci. 2004;95:765–9.

    Article  PubMed  CAS  Google Scholar 

  21. Tochner Z, Mitchell JB, Harrington FS, Smith P, Russo DT, Russo A. Treatment of murine intraperitoneal ovarian ascitic tumor with hematoporphyrin derivative and laser light. Cancer Res. 1985;45:2983–7.

    PubMed  CAS  Google Scholar 

  22. Chekulayeva LV, Chekulayev VA, Shevchuk IN. Active oxygen intermediates in the degradation of hematoporphyrin derivative in tumor cells subjected to photodynamic therapy. J Photochem Photobiol B. 2008;93:94–107.

    Article  PubMed  CAS  Google Scholar 

  23. Huang J, Feng R, Zhu C, Chen Z. Low-MHz frequency effect on a sonochemical reaction determined by an electrical method. Ultrason Sonochem. 1995;2:93–7.

    Article  Google Scholar 

  24. Barati AH, Mokhtari-Dizaji M, Mozdarani H, Bathaie SZ, Hassan ZM. Treatment of murine tumors using dual frequency ultrasound in an experimental in vivo model. Ultrasound Med Biol. 2009;35:756–63.

    Article  PubMed  Google Scholar 

  25. Teicher BA. Tumor model in cancer research. Totawa: Human Press; 2002. p. 407–49.

  26. Barati AH, Mokhtari-Dizaji M. Ultrasound dose fractionation in sonodynamic therapy. Ultrasound Med Biol. 2010;36:880–7.

    Article  PubMed  Google Scholar 

  27. Austerlitz C, de Souza VLB, Campos DMT, Kurachi C, Bagnato C, Sibata C. Enhanced response of the Fricke solution doped with hematoporphyrin under X-rays irradiation. Braz Arch Biol Technol. 2008;51:271–9.

    Article  CAS  Google Scholar 

  28. Bloom-Richardson Grade for Breast Cancer, Cancer Reporting in California: Abstracting and Coding Procedures for Hospitals (California Cancer Reporting System Standards, vol. I). 2007;3–8.

  29. Suslick KS, Flannigan DJ. Inside a collapsing bubble: sonoluminescence and the conditions during cavitation. Annu Rev Phys Chem. 2008;59:659–83.

    Article  PubMed  CAS  Google Scholar 

  30. Wang S, Huang B, Wang Y, Liao L. Comparison of enhancement of pentachlorophenol sonolysis at 20 kHz by dual frequency sonication. Ultrason Sonochem. 2006;13:506–10.

    Article  PubMed  CAS  Google Scholar 

  31. Ciuti P, Dezhkunov NV, Francescutto A, Kulak AL, Iernetti G. Cavitation activity stimulation by low frequency field pulses. Ultrason Sonochem. 2000;7:213–6.

    Article  PubMed  CAS  Google Scholar 

  32. Tang HW, Blankschtein D, Langer R. An investigation of the role of cavitation in low frequency ultrasound mediated transdermal drug transport. Pharm Res. 2002;19:1160–9.

    Article  PubMed  CAS  Google Scholar 

  33. Kanthale PM, Brotchie A, Ashokkumar M, Grieser F. Experimental and theoretical investigations on sonoluminescence under dual frequency conditions. Ultrason Sonochem. 2008;15:629–35.

    Article  PubMed  CAS  Google Scholar 

  34. Hasanzadeh H, Mokhtari-Dizaji M, Bathaie SZ, Hassan ZM. Evaluation of correlation between chemical dosimetry and subharmonic spectrum analysis to examine the acoustic cavitation. Ultrason Sonochem. 2010;17:863–9.

    Article  PubMed  CAS  Google Scholar 

  35. Hasanzadeh H, Mokhtari-Dizaji M, Bathaie SZ, Hassan ZM, Nilchiani V, Goudarzi H. Enhancement and control of acoustic cavitation yield by low level dual frequency sonication: a subharmonic analysis. Ultrason Sonochem. 2011;18:394–400.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors would like to thank Dr. Shahbazfar from Tabriz University for the histological study. This work was supported in part by the Iran National Science Foundation (INSF).

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Correspondence to Manijhe Mokhtari-Dizaji.

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Alamolhoda, M., Mokhtari-Dizaji, M., Barati, A.H. et al. Comparing the in vivo sonodynamic effects of dual- and single-frequency ultrasound in breast adenocarcinoma. J Med Ultrasonics 39, 115–125 (2012). https://doi.org/10.1007/s10396-012-0348-9

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  • DOI: https://doi.org/10.1007/s10396-012-0348-9

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